Peptidic oxytocin receptor agonists include the natural hormone oxytocin, and carbetocin.

Oxytocin is a potent uterotonic agent, clinically used to induce labour, and has been shown to enhance the onset and maintenance of lactation (Gimpl et al., Physiol. Rev., 81, (2001), 629-683; Ruis et al., BMJ, 283, (1981), 340-342). Carbetocin (1-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin) is also a potent uterotonic agent clinically used for the control of uterine atony and excessive bleeding. Further research indicates that oxytocin agonists are useful for the treatment of inflammation and pain, including abdominal and back pain (Yang, Spine, 19, (1994), 867-71); sexual dysfunction, both male (Lidberg et al., Pharmakopsychiat., 10, (1977), 21-25) and female (Anderson-Hunt, et al., BMJ, 309 (1994), 929); irritable bowel syndrome (IBS; Louvel et al., Gut, 39, (1996), 741-47), constipation and gastrointestinal obstruction (Ohlsson et al., Neurogastroenterol. Motil., 17, (2005), 697-704); autism (Hollander et al., Neuropsychopharm., 28, (2008), 193-98), stress (including Post Traumatic Stress Disorder, PTSD; Pitman et al., Psychiatry Research, 48, 107-117), anxiety (including anxiety disorder) and depression (Kirsch et al., J. Neurosci., 25(49), 11489-93; Waldherr et al., PNAS, 104, (2007), 16681-84); surgical blood loss, the control of post-partum haemorrhage (Fujimoto et al., Acta Obstet. Gynecol., 85, (2006), 1310-14), labor induction and maintenance (Flamm et al., Obstet. Gynecol., 70, (1987) 709-12), wound healing and infection; mastitis and placenta delivery; and osteoporosis. Additionally, oxytocin agonists may be useful for the diagnosis of both cancer and placental insufficiency.
Efforts continue to identify and develop compounds with sufficient potency at the human oxytocin receptor. Analogues of oxytocin have been synthesised. Such analogues are described in Grzonka et al., J. Med. Chem., 26, (1983), 555-559 and J. Med. Chem., 26, (1983), 1786-1787, and in Engstrøm et al., E. J. Pharmacol., 355, (1998), 203-210. Additionally, oxytocin analogues with antagonist activity at the oxytocin receptor have been described in Fragiadaki et al., E. J. Med. Chem., (2007), 799-806.
The present invention may provide potent and long duration of action compounds, providing feasible alternatives and/or improvements in the treatment of, e.g., abdominal pain, irritable bowel syndrome (IBS), autism, erectile dysfunction, female sexual dysfunction, labor induction and maintenance, lactation induction and maintenance, postpartum hemorrhage, Post Traumatic Stress Disorder (PTSD), pain, anxiety, surgical blood loss, cancer diagnostics, constipation, depression, insomnia, mastitis, OB diagnostics (for placental insufficiency), osteoporosis, placenta delivery, and wound healing/inflammation.